Cardiac output and peripheral vascular resistance during normotensive and hypertensive pregnancy - a systematic review and meta-analysis.

BACKGROUND: In-depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. OBJECTIVES: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. SEARCH STRATEGY: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. SELECTION CRITERIA: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non-pregnant reference measurement. Studies including women using antihypertensive medication were excluded. DATA COLLECTION AND ANALYSIS: Pooled mean differences between pregnant and non-pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random-effects model in normotensive and hypertensive pregnancy. Meta-regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. MAIN RESULTS: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min1 ; 95% CI 1.18-1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, -331 dyn·sec-1 ·cm-5 ; 95% CI -384 to -277 dyn·sec-1 ·cm-5 ) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. CONCLUSIONS: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. TWEETABLE ABSTRACT: Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications.

Pregnancy and phaeochromocytoma/paraganglioma: clinical clues affecting diagnosis and outcome - a systematic review.

BACKGROUND: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child. OBJECTIVE: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL. SEARCH STRATEGY: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French. SELECTION CRITERIA: Case reports containing a predefined minimum of clinical data on PPGL and pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis. MAIN RESULTS: Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis. CONCLUSION: Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome. TWEETABLE ABSTRACT: Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.

Effect of pregnancy prolongation in early-onset pre-eclampsia on postpartum maternal cardiovascular, renal and metabolic function in primiparous women: an observational study.

OBJECTIVE: To evaluate the association between deferred delivery in early-onset pre-eclampsia and offspring outcome and maternal cardiovascular, renal and metabolic function in the postpartum period. DESIGN: Observational study. SETTING: Tertiary referral hospital. POPULATION: Nulliparous women diagnosed with pre-eclampsia before 34 weeks' gestation who participated in a routine postpartum cardiovascular risk assessment programme. Women with hypertension, diabetes mellitus or renal disease prior to pregnancy were excluded. METHODS: Regression analyses were performed to assess the association between pregnancy prolongation and outcome measures. MAIN OUTCOME MEASURES: Offspring outcome and prevalence of deviant maternal cardiovascular, renal and metabolic function. RESULTS: The study population included 564 women with a median pregnancy prolongation of 10 days (interquartile range [IQR] 4-18) who were assessed at on average 8 months (IQR 6-12) postpartum. Pregnancy prolongation after diagnosis resulted in a decrease in infant mortality (adjusted odd ratio [aOR] 0.907, 95% CI 0.852-0.965 per day prolongation). This improvement in offspring outcome was associated with an elevated risk of moderately increased albuminuria (aOR 1.025, 95% CI 1.006-1.045 per day prolongation), but not with aberrant cardiac geometry, cardiac systolic or diastolic dysfunction, persistent hypertension or metabolic syndrome. CONCLUSION: Pregnancy prolongation in early-onset pre-eclampsia is associated with improved offspring outcome and survival. These effects do not appear to be deleterious to short-term maternal cardiovascular and metabolic function but are associated with a modest increase in risk of residual albuminuria. TWEETABLE ABSTRACT: Pregnancy prolongation in pre-eclampsia has only a limited effect on postpartum maternal cardiovascular function.

External validation and clinical usefulness of first-trimester prediction models for small- and large-for-gestational-age infants: a prospective cohort study.

OBJECTIVE: To assess the external validity of all published first-trimester prediction models based on routinely collected maternal predictors for the risk of small- and large-for-gestational-age (SGA and LGA) infants. Furthermore, the clinical potential of the best-performing models was evaluated. DESIGN: Multicentre prospective cohort. SETTING: Thirty-six midwifery practices and six hospitals (in the Netherlands). POPULATION: Pregnant women were recruited at <16 weeks of gestation between 1 July 2013 and 31 December 2015. METHODS: Prediction models were systematically selected from the literature. Information on predictors was obtained by a web-based questionnaire. Birthweight centiles were corrected for gestational age, parity, fetal sex, and ethnicity. MAIN OUTCOME MEASURES: Predictive performance was assessed by means of discrimination (C-statistic) and calibration. RESULTS: The validation cohort consisted of 2582 pregnant women. The outcomes of SGA <10th percentile and LGA >90th percentile occurred in 203 and 224 women, respectively. The C-statistics of the included models ranged from 0.52 to 0.64 for SGA (n = 6), and from 0.60 to 0.69 for LGA (n = 6). All models yielded higher C-statistics for more severe cases of SGA (<5th percentile) and LGA (>95th percentile). Initial calibration showed poor-to-moderate agreement between the predicted probabilities and the observed outcomes, but this improved substantially after recalibration. CONCLUSION: The clinical relevance of the models is limited because of their moderate predictive performance, and because the definitions of SGA and LGA do not exclude constitutionally small or large infants. As most clinically relevant fetal growth deviations are related to 'vascular' or 'metabolic' factors, models predicting hypertensive disorders and gestational diabetes are likely to be more specific. TWEETABLE ABSTRACT: The clinical relevance of prediction models for the risk of small- and large-for-gestational-age is limited.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.